rs769574194
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_006567.5(FARS2):c.1066-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
FARS2
NM_006567.5 splice_polypyrimidine_tract, intron
NM_006567.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.796
Genes affected
FARS2 (HGNC:21062): (phenylalanyl-tRNA synthetase 2, mitochondrial) This gene encodes a protein that transfers phenylalanine to its cognate tRNA. This protein localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene can cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 6-5613154-C-G is Benign according to our data. Variant chr6-5613154-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 587664.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FARS2 | NM_006567.5 | c.1066-15C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000274680.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FARS2 | ENST00000274680.9 | c.1066-15C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006567.5 | P1 | |||
FARS2 | ENST00000324331.10 | c.1066-15C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
FARS2 | ENST00000648580.1 | c.1066-15C>G | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247100Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133726
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GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454294Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 723606
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GnomAD4 genome Cov.: 33
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33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Jun 13, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at